Photochemical transformations enable exquisite spatiotemporal control over biochemical processes; however, methods for reliable manipulations of biomolecules tagged with biocompatible photo-sensitive reporters are lacking. Here we created a high-affinity binder specific to a photolytically removable caging group. We utilized chemical modification or genetically encoded incorporation of noncanonical amino acids to produce proteins with photocaged cysteine or selenocysteine residues, which were used for raising a high-affinity monoclonal antibody against a small photoremovable tag, 4,5-dimethoxy-2-nitrobenzyl (DMNB) group. Employing the produced photocage-selective binder, we demonstrate selective detection and immunoprecipitation of a variety of DMNB-caged target proteins in complex biological mixtures. This combined orthogonal strategy permits photocage-selective capture and light-controlled traceless release of target proteins for a myriad of applications in nanoscale assays.

光化学转化使得能够对生化过程进行精确的时空控制，但是，缺少可靠操作标记有生物相容性光敏报道分子的生物分子的方法。在这里，我们创建了一种高亲和力的粘合剂，专门用于可光解的笼型基团。我们利用化学修饰或非规范氨基酸的基因编码并入来产生带有光笼中的半胱氨酸或硒代半胱氨酸残基的蛋白质，这些蛋白质用于引发针对小的可光去除标签4,5-二甲氧基-2-硝基苄基（DMNB）的高亲和力单克隆抗体组。利用产生的光笼选择性粘合剂，我们证明了在复杂生物混合物中多种DMNB笼罩的靶蛋白的选择性检测和免疫沉淀。